Inhibition Of Cell Division Research Articles

Coordination of cell division and chromosome segregation by iron and a sRNA in Escherichia coli

Iron is a vital metal ion frequently present as a cofactor in metabolic enzymes involved in central carbon metabolism, respiratory chain, and DNA synthesis. Notably, iron starvation was previously shown to inhibit cell division, although the mechanism underlying this observation remained obscure. In bacteria, the sRNA RyhB has been intensively characterized to regulate genes involved in iron metabolism during iron starvation. While using the screening tool MAPS for new RyhB targets, we found that the mRNA zapB, a factor coordinating chromosome segregation and cell division (cytokinesis), was significantly enriched in association with RyhB. To confirm the interaction between RyhB and zapB mRNA, we conducted both in vitro and in vivo experiments, which showed that RyhB represses zapB translation by binding at two distinct sites. Microscopy and flow cytometry assays revealed that, in the absence of RyhB, cells become shorter and display impaired chromosome segregation during iron starvation. We hypothesized that RyhB might suppress ZapB expression and reduce cell division during iron starvation. Moreover, we observed that deleting zapB gene completely rescued the slow growth phenotype observed in ryhB mutant during strict iron starvation. Altogether, these results suggest that during growth in the absence of iron, RyhB sRNA downregulates zapB mRNA, which leads to longer cells containing extra chromosomes, potentially to optimize survival. Thus, the RyhB-zapB interaction demonstrates intricate regulatory mechanisms between cell division and chromosome segregation depending on iron availability in E. coli.

Systematic discovery of antibacterial and antifungal bacterial toxins.

Microorganisms use toxins to kill competing microorganisms or eukaryotic cells. Polymorphic toxins are proteins that encode carboxy-terminal toxin domains. Here we developed a computational approach to identify previously undiscovered, conserved toxin domains of polymorphic toxins within 105,438 microbial genomes. We validated nine short toxins, showing that they cause cell death upon heterologous expression in either Escherichia coli or Saccharomyces cerevisiae. Five cognate immunity genes that neutralize the toxins were also discovered. The toxins are encoded by 2.2% of sequenced bacteria. A subset of the toxins exhibited potent antifungal activity against various pathogenic fungi but not against two invertebrate model organisms or macrophages. Experimental validation suggested that these toxins probably target the cell membrane or DNA or inhibit cell division. Further characterization and structural analysis of two toxin-immunity protein complexes confirmed DNase activity. These findings expand our knowledge of microbial toxins involved in inter-microbial competition that may have the potential for clinical and biotechnological applications.

Small peptide SiDVL/RTFLs from foxtail millet inhibit root growth through repressing auxin signaling in transgenic Arabidopsis.

SiDVLs inhibit auxin signaling to regulate root growth by enhancing the expression of Aux/IAAs and reducing the protein accumulation of PINs. The DEVIL/ ROTUNDIFOLIA (DVL/RTFL), a small polypeptide family, is conserved in seed plants and important in regulating plant growth and development. However, the molecular mechanisms remain largely unknown. Here, 27 SiDVLs were identified in foxtail millet genome. Overexpression of three SiDVLs in Arabidopsis (Arabidopsis thaliana) strongly repressed the plant growth, especially the root growth. We demonstrate that overexpression of SiDVLs enhances Auxin/Indole-3-Acetic Acids (Aux/IAAs) transcription, thereby weakening auxin signaling in the roots. Furthermore, SiDVLs reduced the protein levels of the auxin transporters PIN-formed 1 (PIN1), PIN2, and PIN7 in the roots. The impaired auxin signaling reduces the cell division and elongation. In conclusion, SiDVLs suppress cell division and elongation in root by inhibiting auxin signaling and transport, which lead to the reduced root growth.

Enhancing the Safety and Efficacy of Trastuzumab Emtansine (T-DM1) Through Nano-Delivery System in Breast Cancer Therapy.

Trastuzumab emtansine (T-DM1), an antibody-drug conjugate, revolutionizes breast cancer therapy by specifically delivering DM1 to human epidermal growth factor receptor 2 (HER2) overexpressing tumor cells, effectively inhibiting cell division and proliferation. While T-DM1 demonstrates superior efficacy and tolerability, T-DM1-induced thrombocytopenia remains a significant adverse event leading to treatment discontinuation. To address this issue, the study investigates the feasibility of using poly(lactic-co-glycolic acid) (PLGA)nanoparticles as a delivery vehicle to conjugate T-DM1, aiming to alleviate T-DM1-induced thrombocytopenia. The T-DM1-conjugated PLGA nanoparticles (NPs-T-DM1) reduce binding to megakaryocytes without compromising the targeting ability for HER2. Administration of NPs-T-DM1 not only significantly inhibits tumor growth but also reduces damage to megakaryocytes, inhibits T-DM1-induced thrombocytopenia, and remarkably improves the safety of antibody-conjugated drugs. This work presents a promising strategy to enhance the safety and efficacy of T-DM1 in antitumor therapy, offering significant potential for advancing clinical application in HER2-positive breast cancer patients.

Vincristine in Cancer Therapy: Mechanisms, Efficacy, and Future Perspectives.

Cancer remains one of the predominant causes of mortality globally, accounting for over 10 million deaths each year. Despite advancements in medical treatments, the challenge of resistance and treatment failure persists, necessitating innovative approaches. Traditional cancer treatments include surgery, chemotherapy, radiation therapy, and pharmaceutical therapy. In recent years, significant attention has been directed towards plant-derived compounds as potential chemotherapeutic agents and preventive measures against cancer. Vincristine, a distinguished alkaloid derived from plant secondary metabolites, has shown considerable efficacy in cancer treatment. As a member of the antimitotic class of compounds, vincristine disrupts the cell cycle by causing aberrations in microtubule function, thereby inhibiting cell division and proliferation. This mechanism of action positions vincristine as a potent agent against various malignancies. Its role in combination therapy is crucial, as it is often administered in low doses alongside other chemotherapeutic agents to enhance its efficacy and reduce the risk of resistance. In the realm of medicinal chemistry, understanding vincristine's molecular mechanism is paramount. Detailed investigations into its interaction with cellular components can provide insights into its antineoplastic properties. This review aimed to elucidate vincristine's mechanism of action and structure-activity relationship, and summarize current in vitro and in vivo studies evaluating its efficacy. Moreover, it discusses innovative strategies, including nanotechnology-based delivery systems, designed to optimize vincristine formulations. These advanced delivery systems aim to improve bioavailability, target specificity, and minimize systemic toxicity. This comprehensive analysis underscores the critical role of vincristine in contemporary cancer treatment and highlights future directions for research and development in this field.

MiR-200c targeting GLI3 inhibits cell proliferation and promotes apoptosis in non-small cell lung cancer cells.

Lung cancer is a common malignant tumor with low cure rate. It has an easy recurrence and metastasis. This study explored whether miR-200c could regulate the biological behavior of non-small cell lung cancer cells through targeting GLI3. Luciferase reporter gene analysis was used to verify the interaction between miR-200c-3p and GLI3. miR-200c-3p and GLI3 were transiently overexpressed into A549 cells. The cell viability rate was detected by cell counting kit-8, cell invasion ability was detected with Transwell, cell apoptosis and cell cycle was determined by flow cytometry, and the expression of GLI3 was detected using quantitative polymerase chain reaction and Western blot, to verify the effect of the interaction between miR-200c-3p and GLI3 on the cell activities. miR-200c-3p overexpression could inhibit cell viability and invasion, promote apoptosis, induce G0/G1 arrest, and inhibit cell division. GLI3 overexpression could reverse the miR-200c-3p inhibition on cell cycle, reduce the number of cells in the G0/G1 phase and increase the number of cells in the S phase. miR-200c-3p overexpression in A549 cells could inhibit cell viability and invasion, and promote apoptosis. miR-200c-3p could target GLI3 to regulate cell cycle and inhibit cell proliferation.

The role of cornulin (CRNN) in the progression of cutaneous squamous cell carcinoma involving AKT activation in SCL-1.

Cutaneous squamous cell carcinoma (cSCC) is the second most common non-melanoma skin cancer that has been on the rise in recent times, particularly among older individuals. Cornulin (CRNN) is increasingly recognized as an oncogene involved in developing various types of tumors. However, the precise contribution to cSCC remains unclear. Our study observed a significant increase in CRNN expression in cSCC samples compared to healthy skin. CRNN expression in the SCL-1 cell line derived from cSCC was reduced, leading to a halt in cell growth during the transition from the G1 phase to the S phase. This reduction inhibits cell division, promotes cell death, and decreases cell invasion and migration. CRNN overexpression has been found to enhance cell growth and prevent cells from undergoing natural cell death, and the cancer-promoting effects of CRNN are linked to AKT activation. Using a mouse xenograft model, we demonstrated that the inhibition of CRNN led to a decline in cSCC tumor growth in a living organism, providing evidence of CRNN's involvement in cSCC occurrence and development. This study establishes a foundation for evaluating the effectiveness of CRNN in treating cSCC, enabling further investigation in this area.

Disruption of salt bridge interactions in the inter-domain cleft of the tubulin-like protein FtsZ of Escherichia coli makes cells sensitive to the cell division inhibitor PC190723.

FtsZ forms a ring-like assembly at the site of division in bacteria. It is the first protein involved in the formation of the divisome complex to split the cell into two halves, indicating its importance in bacterial cell division. FtsZ is an attractive target for developing new anti-microbial drugs to overcome the challenges of antibiotic resistance. The most potent inhibitor against FtsZ is PC190723, which is effective against all strains and species of Staphylococcus, including the methicillin- and multi-drug-resistant Staphylococcus aureus and strains of Bacillus. However, FtsZs from bacteria such as E. coli, Streptococcus, and Enterococcus were shown to be resistant to this inhibitor. In this study, we provide further evidence that the three pairwise bridging interactions, between residues S227 and G191, R307 and E198 and D299 and R202, between S7, S9, S10 β-strands and the H7 helix occlude the inhibitor from binding to E. coli FtsZ. We generated single, double and triple mutations to disrupt those bridges and tested the effectiveness of PC190723 directly on Z-ring assembly in vivo. Our results show that the disruption of S227-G191 and R307-E198 bridges render EcFtsZ highly sensitive to PC190723 for Z-ring assembly. Ectopic expression of the double mutants, FtsZ S227I R307V results in hypersensitivity of the susceptible E. coli imp4213 strain to PC190723. Our studies could further predict the effectiveness of PC190723 or its derivatives towards FtsZs of other bacterial genera.

Gallic acid regulates primary root elongation via modulating auxin transport and signal transduction.

Gallic acid is an important secondary metabolite in plants, with great value in medicine, food, and chemical industry. However, whether and how this widely existing natural polyphenolic compound affects the growth and development of plants themselves remains elusive. In this study, we revealed that exogenous application of gallic acid has a dual effect on the elongation of primary root in Arabidopsis. While lower concentrations of gallic acid slightly stimulate primary root growth, excessive gallic acid profoundly reduces primary root length and root meristem size in a dose-dependent manner, probably via suppressing cell division in root meristem as indicated by CYCB1;1::GUS. Moreover, as suggested by the DR5::GFP line analysis and confirmed by the LC-MS assay, auxin contents in root tips were dramatically decreased upon excessive gallic acid treatment. Additional application of IAA partially rescued the shortened primary root and root meristem upon excessive gallic acid treatment, suggesting that auxin is required for excessive gallic acid-caused root growth inhibition. Then, we further revealed that excessive gallic acid down-regulated the expression of auxin transporters PIN1, PIN2, PIN3, and PIN7, and triple mutant pin1 pin3 pin7 exhibited a reduced sensitivity to gallic acid treatment. Meanwhile, excessive gallic acid decreased the degradation of AXR3/IAA17 protein as revealed by HS::AXR3NT-GUS reporter line. Auxin signaling mutant tir1 afb2 afb3 and axr3-3 were also less sensitive to excessive gallic acid treatment in terms of primary root length and root meristem size. Taken together, these findings suggested that excessive gallic acid inhibits primary root growth by modulating auxin transport and signaling in Arabidopsis.

Cell-to-cell signaling in cell populations with large cell size variability.

Sizes of multiple cells vary when they communicate with each other. Differences in cell size result in variations in the cell surface area and volume, as well as the number of enzymes and receptors involved in signal transduction. Although heterogeneity in cell size may inhibit uniformity in signaling, cell-to-cell signaling is still possible. The outcome when cell size changes to an extreme degree remains unclear. Hence, we inhibited cell division in Dictyostelium cells, a model organism for signal transduction, to gain insights into the consequences of extreme cell size variations. Measurements of cell signals in this population using fluorescence microscopy indicated that the giant cells can communicate with normal-sized cells by suppressing the signal level. Simulations of signal transduction based on the FitzHugh-Nagumo model also suggested similar results.Our findings suggest that signaling mechanism homogenizes cell-to-cell signaling in response to cell size.

From Ficus recemosa Leaf Galls to Therapeutic Silver Nanoparticles: Antibacterial and Anticancer Applications.

The synthesis of silver nanoparticles (AgNPs) using environmentally friendly methods has become increasingly important due to its sustainability and cost-effectiveness. This study investigates the green synthesis of AgNPs using gall extracts from the plant Ficus recemosa, known for its high phytochemical content. The formation of AgNPs was verified through multiple analytical techniques, including UV-Vis spectroscopy, Fourier-transform infrared (FTIR) spectroscopy, transmission electron microscopy (TEM), zeta potential analysis, and dynamic light scattering (DLS). The UV-Vis spectroscopy results displayed a distinct surface plasmon resonance peak indicative of AgNP formation. FTIR analysis revealed specific interactions between silver ions and phytochemicals in the gall extract, while TEM images confirmed the nanoscale morphology and size of the synthesized particles. Zeta potential and DLS analyses provided insights into the stability and size distribution of the AgNPs, demonstrating good colloidal stability. Biological properties of the AgNPs were assessed through various assays. Antimicrobial activity was tested using the disc diffusion method against Escherichia coli and Staphylococcus aureus, showing significant inhibitory effects. The anticancer potential was evaluated using the trypan blue exclusion assay on Dalton's Lymphoma Ascites (DLA) cells, revealing considerable cytotoxicity. Additionally, antimitotic activity was studied in the dividing root cells of Allium cepa, where the AgNPs significantly inhibited cell division. This research highlights the effective use of F. recemosa gall extracts for the green synthesis of AgNPs, presenting an eco-friendly approach to producing nanoparticles with strong antimicrobial, anticancer, and antimitotic properties. The promising results suggest potential applications of these biogenic AgNPs in medical and agricultural sectors, paving the way for further exploration and utilization.

Double-Heading Produces Larger Fruit via Inhibiting EjFWLs Expression and Promoting Cell Division at the Early Stage of Loquat Fruit Development

Loquat is an evergreen fruit crop which blooms from autumn–winter, and supports human beings with juicy fruit from late spring to early summer. However, the most traditional cultivars of this crop produce small fruit and bear a much lower yield than its relatives like apple, pear and peach. Large-size cultivars have long been a cherished aim of breeders for improving the production yield of loquat. Agronomic practices like panicle thinning, fruit thinning, growth regulator application, fertilization and so on are easier and more accessible ways for growers to produce large-size loquat fruit on existing production trees. Here, we develop a novel pruning method with an annual double back-cut, which provides vigorous shoot with more leaves and thicker branches for bearing much larger loquat fruit. Cellular observation determined that the vigorous shoot training method motivated cell division to produce larger loquat fruit, and that most of these cell layers were proliferated before the appearance of flower blossoms. Gene expression data of four development stages showed that EjFWL1 and EjFWL2 were notably downregulated in flower buds of the vigorously pruned tree. The data here further confirmed that the cell division capacity during flower development greatly influenced both the flower and fruit size of loquat. More importantly, we developed a novel pruning method to inhibit cell division repressors, promote cell proliferation and enlarge fruit size in loquat.

The novel drug candidate VOMG kills Mycobacterium abscessus and other pathogens by inhibiting cell division

The incidence of lung infections is increasing worldwide in individuals suffering from cystic fibrosis and chronic obstructive pulmonary disease. Mycobacterium abscessus is associated with chronic lung deterioration in these populations. The intrinsic resistance of M. abscessus to most conventional antibiotics jeopardizes treatment success rates. To date, no single drug has been developed targeting M. abscessus specifically. The objective of this study was to characterize VOMG, a pyrithione-core drug-like small molecule, as a new compound active against M. abscessus and other pathogens. A multi-disciplinary approach including microbiological, chemical, biochemical and transcriptomics procedures was used to validate VOMG as a promising anti-M. abscessus drug candidate. To the authors' knowledge, this is the first study to report the in-vitro and in-vivo bactericidal activity of VOMG against M. abscessus and other pathogens. Besides being active against M. abscessus biofilm, the compound showed a favourable pharmacological (ADME-Tox) profile. Frequency of resistance studies were unable to isolate resistant mutants. VOMG inhibits cell division, particularly the FtsZ enzyme. VOMG is a new drug-like molecule active against M. abscessus, inhibiting cell division with broad-spectrum activity against other microbial pathogens.

Jasmonate signaling modulates root growth by suppressing iron accumulation during ammonium stress.

Plants adapt to changing environmental conditions by adjusting their growth physiology. Nitrate (NO3-) and ammonium (NH4+) are the major inorganic nitrogen forms for plant uptake. However, high NH4+ inhibits plant growth, and roots undergo striking changes, such as inhibition of cell expansion and division, leading to reduced root elongation. In this work, we show that high NH4+ modulates nitrogen metabolism and root developmental physiology by inhibiting iron (Fe)-dependent Jasmonate (JA) signaling and response in Arabidopsis (Arabidopsis thaliana). Transcriptomic data suggested that NH4+ availability regulates Fe and JA-responsive genes. High NH4+ levels led to enhanced root Fe accumulation, which impaired nitrogen balance and growth by suppressing JA biosynthesis and signaling response. Integrating pharmacological, physiological, and genetic experiments revealed the involvement of NH4+ and Fe-derived responses in regulating root growth and nitrogen metabolism through modulation of the JA pathway during NH4+ stress. The JA signaling transcription factor MYC2 directly bound the promoter of the NITRATE TRANSPORTER 1.1 (NRT1.1) and repressed it to optimize the NH4+/Fe-JA balance for plant adaptation during NH4+ stress. Our findings illustrate the intricate balance between nutrient and hormone-derived signaling pathways that appear essential for optimizing plant growth by adjusting physiological and metabolic responses during NH4+/Fe stress.

Penicillin-binding protein 3 sequence variations reduce susceptibility of Pseudomonas aeruginosa to β-lactams but inhibit cell division.

β-lactam antibiotics, which inhibit penicillin-binding protein 3 (PBP3) that is required for cell division, play a key role in treating P. aeruginosa infections. Some sequence variations in PBP3 have been associated with β-lactam resistance but the effects of variations on antibiotic susceptibility and on cell division have not been quantified. Antibiotic efflux can also reduce susceptibility. To quantify the effects of PBP3 variations on β-lactam susceptibility and cell morphology in P. aeruginosa. Nineteen PBP3 variants were expressed from a plasmid in the reference strain P. aeruginosa PAO1 and genome engineering was used to construct five mutants expressing PBP3 variants from the chromosome. The effects of the variations on β-lactam minimum inhibitory concentration (MIC) and cell morphology were measured. Some PBP3 variations reduced susceptibility to a variety of β-lactam antibiotics including meropenem, ceftazidime, cefepime and ticarcillin with different variations affecting different antibiotics. None of the tested variations reduced susceptibility to imipenem or piperacillin. Antibiotic susceptibility was further reduced when PBP3 variants were expressed in mutant bacteria overexpressing the MexAB-OprM efflux pump, with some variations conferring clinical levels of resistance. Some PBP3 variations, and sub-MIC levels of β-lactams, reduced bacterial growth rates and inhibited cell division, causing elongated cells. PBP3 variations in P. aeruginosa can increase the MIC of multiple β-lactam antibiotics, although not imipenem or piperacillin. PBP3 variations, or the presence of sub-lethal levels of β-lactams, result in elongated cells indicating that variations reduce the activity of PBP3 and may reduce bacterial fitness.

Cytological and Transcriptome Analyses Provide Insights into Persimmon Fruit Size Formation (Diospyros kaki Thunb.).

Persimmon (Diospyros kaki Thunb.) fruit size variation is abundant. Studying the size of the persimmon fruit is helpful in improving its economic value. At present, the regulatory mechanism of persimmon fruit size formation is still unclear. In this study, the mechanism of fruit size formation was investigated through morphological, cytological and transcriptomic analyses, as well as exogenous ethrel and aminoethoxyinylglycine (AVG: ethylene inhibitor) experiments using the large fruit and small fruit of 'Yaoxianwuhua'. The results showed that stages 3-4 (June 11-June 25) are the crucial morphological period for differentiation of large fruit and small fruit in persimmon. At this crucial morphological period, the cell number in large fruit was significantly more than that in small fruit, indicating that the difference in cell number is the main reason for the differentiation of persimmon fruit size. The difference in cell number was caused by cell division. CNR1, ANT, LAC17 and EB1C, associated with cell division, may be involved in regulating persimmon fruit size. Exogenous ethrel resulted in a decrease in fruit weight, and AVG treatment had the opposite effect. In addition, LAC17 and ERF114 were upregulated after ethrel treatment. These results indicated that high ethylene levels can reduce persimmon fruit size, possibly by inhibiting cell division. This study provides valuable information for understanding the regulation mechanism of persimmon fruit size and lays a foundation for subsequent breeding and artificial regulation of fruit size.

Significance of Triazole in Medicinal Chemistry: Advancement in Drug Design, Reward and Biological Activity.

One of the triazole tautomers, 1,2,4-triazole derivatives, has a wide range of biological activities that suggest its potential therapeutic utility in medicinal chemistry. These actions include anti-inflammatory, anti-cancer, anti-bacterial, anti-tuberculosis, and anti-diabetic effects. Using computational simulations and models, we investigate the structure-activity relationships of 1,2,4-triazoles, showing how various modifications to the triazole core yield a variety of clinical therapeutic benefits. The review highlights the anti-inflammatory effect of 1,2,4-triazoles in relation to their ability to disrupt significant inflammatory mediators and pathways. We present in-silico data that illuminate the triazoles' capacity to inhibit cell division, encourage apoptosis, and stop metastasis in a range of cancer models. This review looks at the bactericidal and bacteriostatic properties of 1,2,4-triazole derivatives, with a focus on their potential efficacy against multi-drug resistant bacterial infections and their usage in tuberculosis therapy. In order to better understand these substances' potential anti-diabetic benefits, this review also looks at how they affect glucose metabolism regulation and insulin responsiveness. Coordinated efforts are required to translate the efficacy of 1,2,4-triazole compounds in preclinical models into practical therapeutic benefits. Based on the information provided, it can be concluded that 1,2,4-triazole derivatives are a promising class of diverse therapeutic agents with potential utility in a range of disorders. Their development and improvement might herald a new era of medical care that will be immensely advantageous to both patients and the medical community as a whole. This comprehensive research, which is further reinforced by in-silico investigations, highlights the great medicinal potential of 1,2,4-triazoles. Additionally, this study encourages more research into these substances and their enhancement for use in pharmaceutical development.

Therapeutic potential of ethoxy mansonone G: A comprehensive exploration of its anticancer actions in breast cancer, colorectal cancer, and non-small cell lung carcinoma.

Mansonone G (MG), a 1,2-naphthoquinones with antiestrogenic, antimicrobial, and anti-adipogenic activities, is derived from the heartwood of Mansonia gagei Drumm. Ethoxy mansonone G (EMG), an essential derivative of MG, has anticancer and antioxidant agent. EMG also has antiestrogen activity and is demonstrated to lower estrogen receptorexpression in endocrine-resistant cells. EMG significantly inhibits cell division, invasion, and anchorage-dependent growth in all cancer types. Through the stimulation of the tumor protein (p53) and extracellular signal-regulated kinase (ERK) signaling cascades, it also causes apoptosis. Moreover, it manifests its anti-cancerous effects in toll-like receptor pathways, c-Jun N-terminal kinase (c-JNK), and nuclear factor kappa B (NF-κB). EMG inhibits the phosphorylation of glycogen synthase kinase (GSK3), Erk, protein kinase B (Akt), and mammalian target of rapamycin (mTOR). By interfering with molecular cascades, EMG significantly reduces the metabolism of cancer cells. This paper focuses on the potential use of EMG in cancer treatment. Moreover, it states the methodology by which specific assays establish the anti-cancerous role of EMG. Breast cancer, non-small cell lung cancer, and colorectal cancer are only a few of the cancers for which EMG was shown to be effective. Through further research, EMG may be developed as a therapeutic solution to complications caused by cancer. This study presents EMG as a novel candidate for cancer therapy, offering a unique combination of pharmacological advantages and mechanistic insights that warrant further exploration and development toward addressing the complexities of cancer treatment.

LRRC56 is an IFT cargo required for assembly of the distal dynein docking complex in Trypanosoma brucei.

Outer dynein arms (ODAs) are responsible for ciliary beating in eukaryotes. They are assembled in the cytoplasm and shipped by intraflagellar transport (IFT) before attachment to microtubule doublets via the docking complex. The LRRC56 protein has been proposed to contribute to ODAs maturation. Mutations or deletion of the LRRC56 gene lead to reduced ciliary motility in all species investigated so far, but with variable impact on dynein arm presence. Here, we investigated the role of LRRC56 in the protist Trypanosoma brucei, where its absence results in distal loss of ODAs, mostly in growing flagella. We show that LRRC56 is a transient cargo of IFT trains during flagellum construction and surprisingly, is required for efficient attachment of a subset of docking complex proteins present in the distal portion of the organelle. This relation is interdependent since the knockdown of the distal docking complex prevents LRRC56's association with the flagellum. Intriguingly, lrrc56-/- cells display shorter flagella whose maturation is delayed. Inhibition of cell division compensates for the distal ODAs absence thanks to the redistribution of the proximal docking complex, restoring ODAs attachment but not the flagellum length phenotype. This work reveals an unexpected connection between LRRC56 and the docking complex.

FvUVI4 inhibits cell division and cell expansion to modulate fruit development in Fragaria vesca

Fruit development is mainly regulated by cell division and expansion. As a negative regulator of the anaphase-promoting complex/cyclosome, UVI4 plays important roles in plant growth and development via coordinating cell cycle. However, currently there is no report on UVI4's functions in regulating fruit development in strawberry. Here, Fragaria vesca homolog FvUVI4 is identified and localizes in the nucleus. FvUVI4 has high gene expression in roots, leaves, flower, buds and green fruits, and low expression in petiole, stem, white and yellow fruit. Fruit development of F. vesca ‘Hawaii4’ is regulated by endoreduplication, and the expression of FvUVI4 is negatively correlated with fruit cell size. Overexpression of FvUVI4 inhibits endoreduplication of leaves, flowers and fruits in both Arabidopsis and F. vesca ‘Hawaii4’, thereby limiting cell expansion and decreasing cell area. Overexpression of FvUVI4 also inhibits mitotic cell cycle leading to decreased cell number, and ultimately affects the growth of leaves, petals and seeds or fruits. Arabidopsis uvi4 mutants obtained via CRISPR-Cas9 technology display opposite growth phenotypes to Arabidopsis and F. vesca ‘Hawaii4’ overexpression lines, which can be restored by overexpression of FvUVI4 in Arabidopsis uvi4 mutants. In conclusion, our study indicates that FvUVI4 inhibits cell expansion and cell division to modulate receptacle development in woodland strawberry.